Flycatcher's Syndrome in
Cavalier King Charles Spaniels

Cavalier
King Charles spaniels are pre-disposed to a disorder called flycatcher's
syndrome*. It is believed to be caused by a mutation in a specific gene which the
dogs have inherited from their parents. There are two apparently conflicting
theories as to its classification: it either is a complex partial epileptic
seizure, due to hallucinations, or it is a compulsive disorder. See
Epilepsy for a
discussion of epileptic seizures in CKCSs.

The flycatcher's-affected cavalier appears to be watching imaginary flies
buzzing in front of its face and then trying to bite the flies. Some affected
dogs may compulsively chase their tails or act as if their ears or paws are
irritated. Episodes may last for several hours, and in severe cases, constantly.
Click here or on the YouTube logo (right) to see videos of cavaliers with
watching and biting imaginary flies.

One study has indicated that
gastrointestinal (GI) diseases may underlie the cause of some cases of
flycatcher's syndrome, so digestive disorder symptoms may be related.

Fly biting behavior also has been identified as a symptom of syringomyelia, a
serious neurological disorder more common in the cavalier King Charles spaniel
than in any other breed. See
Syringomyelia for
information about this disease.

Diagnosing begins by ruling out other causes for the behavior. A video
recording of an episode is helpful to the veterinarian. If epilepsy is the
suspected disorder, advanced imaging, such as magnetic resonance imaging (MRI)
or computed tomography (CT) scans, is necessary to image the brain and enable
the veterinarians to diagnose diseases such as brain tumors or hydrocephalus
(water on the brain) which can cause seizures. Apart from the
electroencephalogram (EEG) or MRI or CT scans, there is no health test for
epilepsy.

Some researchers have suggested that fly catching in cavaliers may be
associated with another disorder unique to the breed, called "idiopathic
asymptomatic thrombocytopenia", an abnormally low number of blood platelets.
Drs. Jens Häggström and Clarence Kvart of
Sweden have noted in a 1997 article that thromboembolic
events in the cerebral circulation of blood may be involved in fly catching. See
Blood Platelets for more information.

In
a
November 2012 study, a team of Canadian researchers studied seven fly-biting
dogs -- including two cavalier King Charles spaniels -- and found that they were suffering from gastrointestinal disorders,
including eosinophilic and lymphoplasmacytic infiltration of the stomach and
small bowel, delayed gastric emptying, and gastroeosophageal reflux. In this
study, the researchers treated the gastrointestinal (GI) diseases and observed
complete resolution of the fly-biting in five of six of the seven dogs,
including a cavalier. The
seventh dog, the other CKCS, was diagnosed with Chiari-like malformation and responded
temporarily to pain management. The researchers concluded that:

"Fly biting behaviour may be caused by an underlying medical disorder, GI disease being the
most common. Resolution of this behaviour is possible following specific
treatment of the underlying medical condition."

Initially, treatment for epilepsy, such as administering an
anti-convulsant
(usually oral phenobarbital and/or bromide) usually is conducted. See
Epilepsy
for a discussion of the treatment of epileptic seizures in CKCSs.

However, it reportedly often has been found that CKCSs with flycatcher's
syndrome will show no response to the anticonvulsant treatment, which would indicate the cause may
be a compulsive disorder. In such cases, selective serotonin reuptake
inhibitors (SSRIs), such as fluoxetine
(Prozac, Sarafem), may be prescribed.

Clomipramine (Anafranil), a tricyclic antidepressant (TCA), inhibits both norepinephrine and
serotonin reuptake. In a
November 2010 Belgium
study, it successfully treated a shadow-chasing cavalier. It has been
suggested to have been associated with the onset of pancreatitis in one
instance. See this February
2009 report.

CAUTION: Fluoxetine and other SSRIs, as well
as clomipramine and other TCAs, can lead to serotonin accumulation and
serotonin syndrome (symptomatically, twitching, tremor, tachycardia, myoclonic
movements, and hyperthermia) in humans when used in combination with monoamine
oxidase inhibitors (MAOIs, which decrease the breakdown of serotonin) or
serotonin reuptake inhibitors, which increase synaptic serotonin concentrations.
Deaths have been reported in humans given clomipramine plus MAOIs—a
well-established interaction.
See this June 2013 report.
Also, high levels of serotonin in cavaliers' blood platelets and mitral valve
tissues have been associated with mitral valve disease. For more information, see
this discussion on our MVD
webpage.

If phenobarbital and clomipramine are combined, phenobarbital accelerates the
metabolism of clomipramine.
See this June 2013 report.

Zonisamide (Zonegram) is an anticonvulsant which in clinical
trials appears to be effective for generalized seizures in dogs. It’s
anti-seizure effect is believed to work through sodium and calcium channels.
Dr. Curtis Dewey has conducted studies of this drug.

Reconcile (fluoxetine hydrochloride) is FDA-approved for canine
separation anxiety and also may be prescribed. However, Reconcile should not be
given to dogs with epilepsy or a history of seizures, or with drugs that lower
the seizure threshold, or with a monoamine oxidase inhibitor (MAOI), or within a
minimum of 14 days of discontinuing therapy with an MAOI.

Daily doses of drugs may take three weeks or longer before a favorable effect
is reached. The examining specialist may recommend that the dog be treated by a
veterinary behaviorist to manage the compulsive disorder by behavior
modification, such as counter-conditioning and positive
reinforcement. Also, it is reported that high protein diets tend to worsen
compulsive disorders, although the reduction of meat or other protein content
may result in only temporary improvement.

Natural supplements may be prescribed as alternatives to anticonvulsants.

In
a
November 2012 study, a team of Canadian researchers studied seven fly-biting
dogs, including two cavaliers, and found that they were suffering from gastrointestinal disorders,
including eosinophilic and lymphoplasmacytic infiltration of the stomach and
small bowel, delayed gastric emptying, and gastroeosophageal reflux. In this
study, the researchers treated the gastrointestinal (GI) diseases and observed
complete resolution of the fly-biting in five (including a cavalier) of six of the seven dogs. The
seventh dog (the other cavalier) was diagnosed with Chiari-like malformation and responded
temporarily to pain management. The researchers concluded that:

"Fly biting behaviour may be caused by an underlying medical disorder, GI disease being the
most common. Resolution of this behaviour is possible following specific
treatment of the underlying medical condition."

November
2012: Some cases of fly catching may be due to gastrointestinal (GI) disease.
In a Canadian study of seven dogs with fly-biting behavior, the researchers
found:

"Many gastrointestinal disorders were found in FB
[fly-biting] dogs which included eosinophilic and lymphoplasmacytic infiltration
of the stomach and small bowel, delayed gastric emptying and gastroeosophageal
reflux. Complete resolution of the FB was observed in 5/6 dogs diagnosed and
specifically treated for the underlying gastrointestinal (GI) disease. One dog
was diagnosed with Chiari malformation and responded temporarily to pain
management. In conclusion, this prospective case series indicates that fly
biting behaviour may be caused by an underlying medical disorder, GI disease
being the most common. Resolution of this behaviour is possible following
specific treatment of the underlying medical condition."

Two of the studied dogs were cavaliers, including the dog diagnosed with
Chiari-like malformation and one of the five dogs diagnosed and successfully
treated for GI disease.

September
2009:Management of Compulsive Disorders. Dr. Clare
Rusbridge and veterinary behaviorists Jon Bowen and
Sarah Heath are conducting a
study of fly catching, tail chasing, shadow watching, and other compulsive
disorders to determine better management strategies. If you have a dog
with a repetitive behavior disorder and able to fill out a questionnaire or
provide urine or saliva samples, please contact Dr. Rusbridge at email
CRusbridge@goddardvetgroup.co.uk

Update on Mitral
Valve Disease. Jens Häggström and Clarence Kvart. Proc. 15th
ACVIM Forum; 1997. Quote: "An interesting observation that may be of comparative
interest is that Cavalier King Charles Spaniels have been shown to have a high
prevalence (30%) of thrombocytopenia and macrothrombocytosis. Humans with MVP
[mitral valve prolapse] tend to have shortened platelet survival times and
thromboembolic episodes primarily in the retinal and cerebral circulation.
Thromboembolic events in the retinal ore cerebral circulation may be involved in
the disturbances described in the breed as 'episodic falling' and 'fly
catching'."

Neurological diseases of the Cavalier King Charles spaniel.
Rusbridge, C. J Small Animal Practice, June 2005, 46(6): 265-272(8). "Fly
catching has previously been classified as a complex partial seizure on the
presumption that the dog was having an hallucination (DeLahunta 1983). However,
it is more likely that this is a compulsive disorder (Luescher 2002).
Classically, the dog acts as if watching, and then catching, a fly. Some may
behave as if their ears or feet are irritated, and some may also chase their
tail. In the author’s experience, the episodes can last hours and are more
common, at least initially, when the owner’s focus is directed away from the
dog; for example, when the family is watching television in the evening. In
severe cases, the dog is occupied in the behaviour almost full time. Compulsive
disorders are compared with obsessivecompulsive disorders in humans and are
poorly understood; it is presumed that there is a neurochemical imbalance (Luescher
2002). Diagnosis is typically made on the basis of clinical history and
elimination of other behavioural, medical and neurological disorders. Ideally
the owner should make a video of the behaviour. If there is doubt as to whether
it is epilepsy then a two- to four-week trial of 3 mg/kg phenobarbital every 12
hours is recommended, adjusting the dose to achieve a serum concentration of 25
mg/l (120 μmol/l). CKCSs with fly catching typically show no
response (DeLahunta 1983). Referral to a veterinary behaviourist is recommended
as there is often a learned component and treatment must involve behaviour
modification in addition to drugs such as selective serotonin reuptake
inhibitors; for example, 2 to 3 mg/kg clomipramine twice daily or 1 to 2 mg/kg
fluoxetine twice daily. Management of compulsive disorders has been reviewed by
Luescher (2002). In principle the behavioural therapy is to train the dog with
positive reinforcement, rewarding it with attention or a small treat, to perform
a desirable behaviour that is incompatible with the compulsive behaviour, such
as lying with its head on the floor between the paws. As soon as the compulsive
behaviour is seen then the dog is immediately distracted and instructed to
perform the desirable behaviour. The reward can be progressively delayed so that
the dog has to remain in the chosen position for increasingly longer times
before the reward is given. If drugs are given then it can take four weeks
before an effect is seen and they must be continued for at least three weeks
after achieving the desired effect before attempting to withdraw them over a
minimum of three weeks. High protein diets, such as those with high meat
content, tend to make compulsive behaviours worse and conversion to a low
protein diet can result in improvement in signs (Brown 1987), although in some
dogs this may be only temporary."

Pancreatitis associated with clomipramine administration in a dog. P H
Kook, A Kranjc, M Dennler, T M Glaus. J. Sm. Anim. Prac. Feb. 2009;50(2):95-98.
Quote: "A three-year-old, male, entire, Yorkshire terrier was presented with
peracute onset of abdominal pain and vomitus. Clinicopathological abnormalities
included severely increased serum lipase activity, immeasurably high serum
trypsin-like immunoreactivity and mild hypocalcaemia. Canine pancreatic lipase
immunoreactivity (cPLI) was intended to be measured, however, the sample got
lost. Ultrasonography revealed a hypoechoic pancreas with small amounts of
peripancreatic fluid and hyperechogenic mesentery. Acute pancreatitis (AP) was
diagnosed and the dog recovered with appropriate therapy within 48 hours.
Clomipramine, a selective serotonin reuptake inhibitor (SSRI) for alleviating
signs of separation anxiety had been given for seven weeks. Two similar, albeit
less severe, episodes associated with previous courses of clomipramine had
occurred eight months earlier that responded to discontinuing clomipramine and
supportive care. As SSRIs are associated with AP in human beings and no other
trigger could be identified, we conclude that clomipramine should be considered
as a potential cause when investigating causes for AP in susceptible breeds or
other dogs presenting with compatible clinical signs."

Serotonin 2A receptor, serotonin transporter and dopamine
transporter alterations in dogs with compulsive behaviour as a promising model
for human obsessive-compulsive disorder. Simon Vermeire, Kurt Audenaert,
Rudy De Meester, Eva Vandermeulen, Tim Waelbers, Bart De Spiegeleer, Jos Eersels,
André Dobbeleir, Kathelijne Peremans. Psychiatry Research: Neuroimaging, online
27 Jan 2012. Quote: "Neuro-imaging studies have shown altered, yet often
inconsistent, serotonergic and dopaminergic neurotransmission in patients with
obsessive–compulsive disorder (OCD). We investigated both serotonergic and
dopaminergic neurotransmission in 9 drug-naïve dogs with compulsive behaviour,
as a potential model for human OCD. Single photon emission computed tomography
was used with 123I-R91150 and 123I-FP-CIT, in combination with 99mTc-ECD brain
perfusion co-registration, to measure the serotonin (5-HT) 2A receptor, dopamine
transporter (DAT) and serotonin transporter (SERT) availability. Fifteen
normally behaving dogs were used as reference group. Significantly lower 5-HT2A
receptor radioligand availability in frontal and temporal cortices (bilateral)
was observed. Further, in 78% of the compulsive dogs abnormal DAT ratios in left
and right striatum were demonstrated. Interestingly, both increased and
decreased DAT ratios were observed. Finally, significantly lower subcortical
perfusion and (hypo)thalamic SERT availability were observed in the compulsive
dogs. This study provides evidence for imbalanced serotonergic and dopaminergic
pathways in the pathophysiology of compulsions in dogs. The similarities with
the altered neurotransmission in human OCD provide construct validity for this
non-induced, natural canine model, suggesting its usefulness for future
investigations of the pathophysiology of human OCD as well as the effectiveness
of psychopharmacological interventions."

Gastrointestinal disorders in dogs with excessive licking of
surfaces. Becuwe-Bonnet V, Belanger M-C, Frank D, Parent J, Helie
P. J.Vet.Behavior. July 2012;7(4):194-204. Quote: "Excessive licking of
surfaces (ELS) refers to licking of objects and surfaces in excess of
duration, frequency, or intensity as compared with that required for
exploration. This behavior is a nonspecific sign and may be the
consequence of several conditions. The objectives of our prospective
clinical study were to characterize ELS behavior in dogs and to examine
the extent to which it may be a sign of an underlying gastrointestinal
(GI) pathology as opposed to a primarily behavioral concern. Nineteen
dogs presented with ELS were included in the licking group and 10
healthy dogs were assigned to a control group. Behavioral, physical, and
neurological examinations were performed before a complete evaluation of
the GI system. Treatment was recommended on the basis of diagnostic
findings. Following initialization of treatment, dogs were then
monitored for 90 days during which their licking behavior was recorded.
GI abnormalities were identified in 14 of 19 dogs in the licking group.
These abnormalities included eosinophilic and/or lymphoplasmacytic
infiltration of the GI tract, delayed gastric emptying, irritable bowel
syndrome, chronic pancreatitis, gastric foreign body, and giardiasis.
Significant improvement in both frequency and duration of the basal ELS
behavior was observed in 10 of 17 dogs (59%). Resolution of ELS occurred
in 9 of 17 dogs (53%). Based on video analysis, it was found that ELS
dogs were not significantly more anxious than the dogs in control group
in the veterinary context. In conclusion, GI disorders should be
considered in the differential diagnosis of canine ELS."

Prospective Medical Evaluation of 7 Dogs Presented with Fly Biting. D.
Frank, MC Bélanger, V. Bécuwe-Bonnet, J. Parent. 22nd ECVIM-CA Congress.
Can Vet J. 2012 December;53(12):1279–1284. (See, also, J.Vet.Intern.Med. Nov. 2012; 26(6):1505–1538.) Quote: "Fly snapping, fly-biting
or jaw snapping are names given to a syndrome in which dogs appear to be
watching something then suddenly leaping and snapping at it. Fly-biting dogs are
generally referred to neurologists or behaviourists because the abnormalities
are often interpreted as focal seizures or as obsessive compulsive disorder
(OCD). There is one published case report of fly biting presumably caused by
dietary intolerance in a Cavalier King Charles Spaniel. The
aims of this case series were 1) to characterize fly biting, 2) perform a
complete medical evaluation of dogs presented with fly biting, and 3) evaluate
the outcome of this behaviour following appropriate treatment of the underlying
medical condition.Seven dogs presented for fly-biting behaviour (FB) were
assessed. ... Our study group included 4 neutered males and 3 females (2 intact,
1 spayed). Four breeds (2 cavalier King Charles spaniels; 1
miniature schnauzer; 1 Boston terrier; 1 Bernese mountain dog), and 2 mixed
breeds, both listed as crosses of Bernese mountain dogs were presented.
... All dogs underwent a complete medical and behavioural history as well
as physical and neurological examinations. Further investigation was performed
if an abnormality was found on examination or if the history was suggestive of
an underlying problem. Based on clinical presentation, physical examination,
neurologic examination, and laboratory test results, a diagnosis was made and a
specific treatment recommended. Response to treatment was monitored and
evaluated following phone conversations with owners at day 30, 60 and 90 from
onset of treatment. Many gastrointestinal disorders were found in FB dogs which
included eosinophilic and lymphoplasmacytic infiltration of the stomach and
small bowel, delayed gastric emptying and gastroeosophageal reflux. Complete
resolution of the FB was observed in 5/6 dogs diagnosed and specifically treated
for the underlying gastrointestinal (GI) disease [including one cavalier
King Charles spaniel]. One dog [cavalier King Charles spaniel] was diagnosed with Chiari malformation and responded temporarily to pain management. In conclusion,
this prospective case series indicates that fly biting behaviour may be caused
by an underlying medical disorder, GI disease being the most common. Resolution
of this behaviour is possible following specific treatment of the underlying
medical condition."

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